Andrographolide attenuates viral myocarditis through interactions with the IL‑10/STAT3 and P13K/AKT/NF‑κβ signaling pathways

Abstract

As a cardiac disease caused by the inflammation of the heart muscle, viral myocarditis (VMC) causes dilated cardiomyopathy, congestive heart failure and even death. With anti-inflammatory activities, andrographolide has been used in the treatment of various human diseases. In the present study, therapeutic effects of andrographolide on VMC were investigated using a VMC mouse model. Measurement of physiological indexes and echocardiographic examination was performed to explore the effects of andrographolide on cardiac function in mice with VMC. Levels of TNF-α, hs-CRP and cTnl in serum were measured by enzyme-linked immunosorbent assay (ELISA). Effects of andrographolide on the expression of L-10, STAT3, NF-κβ p65 and NF-κβ p50 were investigated by western blot analysis. Results indicated that andrographolide treatment reduced serum levels of TNF-α, hs-CRP and cTnl, increased the expression levels of IL-10 and STAT3 and reduced the expression levels of NF-κβ p65 and NF-κβ p50 and the phosphorylation levels of phosphoinositide 3-kinase (P13K) and AKT in the heart tissues of mice with VMC. In addition, andrographolide also increased the expression level of Iκβα in heart tissue. Therefore, it was concluded that andrographolide may inhibit the progression of VMC by interacting with the IL-10/STAT3 and NF-κβ signaling pathways.

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches

“…In another project, the author demonstrated that andrographolide markedly improved adverse cardiac remodeling induced by myocardial infarction and ameliorated contractile function in C57/BL6 mice with LAD ligation, which the specific mechanism may be related to the enhancement of Nrf2 signaling pathway (Xie et al, 2020). Additionally, andrographolide was reported to lessen the serum levels of tumor necrosis factor‐α (TNF‐α), enhance the expression of interleukin‐10 (IL‐10) and signal transducers and activators of transcription 3 (STAT3), exhaust the expression levels of NF‐p65 and NF‐p50, as well as the phosphorylation levels of phosphoinositide 3‐kinase (P13K) in the heart tissues of mice with viral myocarditis (VMC) (Zhao, Wang, Li, & Dong, 2018). Chronic inflammation, oxidative stress and dyslipidemia are the cardinal factors of atherosclerosis.…”

Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective

“…176 Andrographolide could also impede IL-10/STAT3 signaling pathways, thereby alleviating viral myocarditis in mice. 177 In a separate study, andrographolide decreased LPS-induced inflammation responses and calcium in primary rat myocardium microvascular endothelial cells. 178 In macrophages, andrographolide also prevented oxidized LDL-induced cholesterol buildup and foam cell production.…”

“…Recently, andrographolide was certified to inhibit human aortic valve interstitial cell calcification 176 . Andrographolide could also impede IL‐10/STAT3 signaling pathways, thereby alleviating viral myocarditis in mice 177 . In a separate study, andrographolide decreased LPS‐induced inflammation responses and calcium in primary rat myocardium microvascular endothelial cells 178 .…”

Andrographolide, a natural anti-inflammatory agent: An Update

“…Andrographolide treatment can reduce plasma TNF-α, IL-17 and myosin antibody levels, increase IL-10 levels, and reduce the infiltration of CD3 + and CD14 + positive cells in myocardial tissue in autoimmune myocarditis rats; the anti-inflammatory activity is relevant to the suppression of the PI3K/Akt pathway ( Zhang et al, 2019b ). Andrographolide may improve viral myocarditis by inhibiting the increase in serum TNF-α, hs-CRP and cTnI levels caused by viral myocarditis, activating the IL-10/STAT3 anti-inflammatory pathway, and inhibiting the PI3K/AKT/NF-κB pathway ( Zhao et al, 2018 ).…”